A powerful new genetic test that scans for rare childhood diseases is providing faster and more conclusive results than ever before. The test examines the entire genome to identify the single gene mutation that led to the disorder.

When Calvin Lapidus was eight months old, his mother Audrey suspected he was not developing normally, even though his doctors said he was.

“By eight months he wasn’t sitting up on his own," she recalled. "He wasn’t rolling over on his own and he was just missing his milestones.”

He described the typical scenario: “Children come in with a set of symptoms, a set of problems, a set of issues, and it’s very difficult for physicians to say which one of 5,000 diseases this patient has.”

Some conditions are so rare that a physician may have only seen a few, if any, cases in his or her practice.

Sequencing DNA

The team at the Center extracted and sequenced DNA from blood samples from Calvin and his parents. Then they scanned all the genes simultaneously to find the single mutation that caused the disorder.

Nelson said that on average every location in the genome is examined and re-examined 100 times.

“What that means is that we see 50 of the DNA variants that you got from your mom," he said. "We see 50 of the DNA variants that you got from your dad at every single base position in the exome, or in the protein coating part of the genome.”

“The likelihood for errors is very, very low because of the oversampling,” he added.

Of the 5,000 rare genetic diseases the exome sequencing can identify, Pitt-Hopkins Syndrome matched Calvin’s symptoms. He is among some 500 known cases marked by developmental delay and intellectual disability.

Baffling cases, solved

Since that diagnosis, 814 patients whose condition had previously baffled doctors have been tested using the new protocol. According to a study in the Journal of the American Medical Association, among the most complex cases like Calvin’s, 40 percent received a definitive diagnosis, compared to 5 percent just 20 years ago. Nelson expects those results to improve, which he said can give families renewed hope for treatment.

“For a subset of the kids, we can take that genetic information and indeed develop new therapies," he said. "As we diagnose these kids earlier on in life, we will be able to start them on some of these upcoming therapies much earlier in life, and that will probably make it so that it will have a much bigger impact throughout their life."

For Calvin's family, the diagnosis -- while painful -- ended a period of uncertainty.

“The diagnosis has certainly helped me prepare for the future as far as knowing what to expect," said Audrey Lapidus. "But Calvin is a naturally happy kid. He’s really easy going. He pretty much likes everything. Most of all he loves the people. He loves hugs. He loves his sister. And eight-year-old sister Sadie loves him back, entertaining him with songs and dances.

While Calvin may never sing back, he is slowly learning to walk. And the Lapidus family has taken steps to help others by creating the Pitt Hopkins Research Foundation dedicated to finding a treatment and cure for the rare disease.